Principal Investigator: Anastos, Kathryn/Sharma Anjali PROJECT SUMMARY/ABSTRACT With increasingly effective universal antiretroviral therapy (ART), people living with HIV (PLWH) may now live nearly normal lifespans. With that success however, comes a series of chronic HIV-related comorbidities, whose mechanisms are poorly understood, but thought to be related to inflammation and immune activation. As PLWH age, they are experiencing this high burden of non-AIDS comorbidities at younger than expected age, including cardiovascular and metabolic diseases, cancers, and neurocognitive and functional impairment - leading some to suggest that HIV may both accentuate AND accelerate aging. The Women's Interagency HIV Study (WIHS) and the Multicenter AIDS Cohort Study (MACS) cohorts, with long-term follow up over 25 and 35 years provide the ability to measure the onset, progression and impact of HIV-related comorbid disease and provide a platform for critically important translational studies of pathogenesis in cardiovascular disease (CVD), human papillomavirus (HPV), aging, and HIV-disease progression. As these two highly successful and critically important cohorts merge, the Bronx Clinical Research Site (CRS) will support the new Combined Cohort Study (CCS) in an effort to understand and advance the study of HIV infection and its treatment, with a focus on HIV-related comorbidities and aging with HIV. The Bronx CRS will provide scientific leadership to the CCS in three specific areas: CVD, microbiome studies, and HPV infection and disease. In particular, the Bronx CRS will provide innovative scientific leadership in studying CVD among PLWH with a longitudinal echocardiography study and a high-caliber Echo Reading Center, including cutting-edge cardiovascular imaging, and the study of CVD in relation to inflammatory markers, metabolomics, and microbiome among PLWH. The Bronx CRS will continue to follow our large numbers of well-characterized persons living with and without HIV, as well as recruit primarily racial and ethnic minority men and women with or at-risk for HIV to reflect our local NYC HIV epidemic, thus allowing us to investigate the impact of age, sex, race/ethnicity, and health disparities on HIV disease progression and its relation to comorbid illnesses across the lifespan. The value of these studies goes far beyond the United States, to inform the global HIV epidemic, and care of PLWH.